Moth-eaten Fibers Research Articles

A benign congenital myopathy in an inbred Samaritan family

We describe a novel form of myopathy in a mother and her two daughters from an inbred Samaritan family. The patients displayed severe neonatal hypotonia, lethargy and dysmorphic features. Motor milestones were delayed; however, the hypotonia and muscle weakness gradually improved during the first 2 years of life and independent walking was achieved by 18 months. The mother at the age of 23 years shows myopathic facies and minimal proximal weakness. Her intelligence is normal. Her muscle biopsy revealed central nuclei and disruption of the intermyofibrillary network with moth eaten and spiral fibers. Mutations in SMN, MTM1 and the myotonic dystrophy genes were excluded. We suggest this is a new benign form of congenital myopathy. Inheritance is probably autosomal recessive.

Blood Supply and Oxidative Metabolism in Muscle Biopsies of Female Cleaners With and Without Myalgia

Pathomechanisms of work-related myalgia are poorly understood. Myalgia is thought to be caused by excitation of nociceptors present in the muscular tissue but not in the muscle fiber itself. Muscle contraction in combination with hypoxia is known to excite nociceptors. Morphologic analysis can contribute to the knowledge of the excitation of nociceptors. This study thoroughly examines the morphology of the trapezius muscle's capillary supply and signs of disturbed oxidative metabolism to understand their role in work-related myalgia. Surgical trapezius muscle biopsies were obtained from 25 female cleaners with long-standing work-related myalgia, 25 female cleaners without trapezius myalgia, and 21 healthy teachers. Enzyme and immunohistochemical stainings were performed to highlight fibers with aberrant intermyofibrillar patterns, indicating a disturbed oxidative metabolism (also known as moth-eaten fibers) and a disturbed capillary supply of different fibers. A significantly lower number of capillaries per fiber area in cleaners suffering from myalgia compared with cleaners without trapezius myalgia was found. Moth-eaten fibers were found in the 3 groups, but these fibers were significantly more prevalent in the groups of cleaners than in the healthy teacher group. This work indicates that the capillary supply of trapezius is affected in work-related trapezius myalgia. More studies are needed to understand possible mechanisms that would explain the occurrence of moth-eaten fibers.

SKELETAL MUSCLE ULTRASTRUCTURAL CHANGES IN ENDURANCE ATHLETES WITH CHRONIC FATIGUE

INTRODUCTION: This case series describes twenty endurance-trained athletes who reported with signs of chronic fatigue. All reported progressive decline in athletic performance, decreased ability to tolerate high mileage training, recurrent bouts of flu like symptoms and muscular fatigue on exercising. METHODS: All subjects' skeletal muscle structure (light and electron microscopic analysis of vastus lateralis muscle biopsy sample) and function (VO2max, isometric peak force output of quadriceps and vertical jump height) was assessed. RESULTS: No abnormalities were detected on routine medical examination and physical performance testing however, 90% of the athletes tested positive for previous Epstein Barr virus infection. Histological examination of the muscle biopsy showed that 69% of athletes presented with extensive subsarcolemmal mitochondrial aggregations, 38% with internal nuclei, 50% with fibre size variation, 25% with necrotic or regenerated fibres and 75% with abnormal moth eaten fibres. Electron microscopic analysis revealed 66% of the athletes had myofibrillar degeneration, 58% had enlarged mitochondria, 33% showed Z disc streaming and 75% showed increased lipid and glycogen deposits. Subjects' VO2max and isometric peak force output values were well within the normal range for age and gender matched individuals. CONCLUSIONS: All athletes presented with ultra structural skeletal muscle abnormalities, which may be responsible for their fatigue. It is possible that the skeletal muscle abnormalities may have resulted from previous viral infections or from a high mileage training and racing history.

WRIST EXTENSOR MUSCLE PATHOLOGY IN LATERAL EPICONDYLITIS

The morphology of the extensor carpi radialis brevis (ECRB) muscle was investigated in 20 patients with longstanding lateral epicondylitis. Muscle biopsies were obtained from the proximal or distal portion of the ECRB and analysed by enzyme- and immunohistochemical methods. Morphological abnormalities were significantly more frequent in patients than controls and included moth-eaten fibres, fibre necrosis and signs of muscle fibre regeneration as well as higher percentages of the fast-twitch oxidative (type 2A) fibre type. Changes were equally distributed proximally and distally. It is concluded that these changes, directly or indirectly, may reflect the cumulative effect of mechanical and/or metabolic overload and that decreased muscular performance in patients with lateral epicondylitis may be due to both elbow pain and physical damage to the ECRB muscle.

Complex I defect in muscle from patients with Huntington's disease.

We found a variable defect of complex I of the mitochondrial respiratory chain, ranging in severity from 25% to 63% of control values, in muscle of patients with Huntington's disease (HD). The most severe defect was observed in the patient with the greatest expansion of CAG triplets. Muscle morphology showed myopathic changes such as moth-eaten fibers, angulated fibers, increased subsarcolemmal oxidative activities, or an increased number of enlarged mitochondria with abnormal cristae. Multiple mitochondrial DNA deletions were found by polymerase chain reaction (PCR) analysis in muscle of the patient with the most severe defect of complex I. Our data further support the involvement of energetic defects and oxidative damage in muscle of patients with HD.

Limb-girdle muscular dystrophy: Clinical and pathologic reevaluation

To better define limb-girdle muscular dystrophy (LGMD), we examined 58 patients clinically and pathologically who fulfilled the criteria for LGMD and had normal dystrophin expression in their muscle biopsies. Only 27.6% of patients had evidence of inheritance. The onset of disease varied from 2 to 58 years of age, averaging 17.2 years. The disease progression also differed from patient to patient. In addition to evidence of muscle fiber necrosis and regeneration, in all muscle biopsies there were fibers with architectural changes of disorganized intermyofibrillar networks including moth-eaten (100%), lobulated (40%), whorled (17%) and targetoid (8%) fibers. The lobulated fibers which have never been reported in Duchenne muscular dystrophy (DMD) were seen in the advanced stages of LGMD, although the significance of such fibers remains unknown. On immunohistochemical examination, dystrophin-associated proteins (DAPs) and laminin were normally expressed along the surface membrane of muscle fibers, including the lobulated fibers.

Morphologic Features of the Myopathy Associated With Chronic Renal Failure

Our previous studies indicate that impaired function of skeletal muscle limits the exercise tolerance of patients with end-stage renal failure who are either maintained on dialysis or undergo renal transplantation. To study the morphology of the condition, muscle biopsies were performed on eight patients with renal failure-associated myopathy. Control samples were taken from seven healthy athletes undergoing knee surgery and from five otherwise healthy but untrained subjects. Tissues were examined by routine light and transmission electron microscopy. Histochemical staining of frozen sections for myosin adenosine triphosphatase and quantitative computer-assisted morphometry of the fiber type and size was performed. The mean (+/- SD) size for type I fibers in patients was 61.2 +/- 11.8 microns, while type II fibers measured 46.7 +/- 11.4 microns. The mean percentage of type II fibers was 67% +/- 12%. These values are within the normal population range and were not different from controls. Significant changes were found on light microscopy of patient samples. These included fiber splitting, internalized nuclei, nuclear knots, moth-eaten fibers, fiber degeneration and regeneration, increased content of lipid droplets, and fiber-type grouping. Electron microscopy showed a large variety of nonspecific abnormalities, including mitochondrial changes, Z-band degeneration, myofilament loss, and accumulation of intracellular glycogen. Ten of 12 control subjects showed no such changes; minor abnormalities were noted on both light and electron microscopy in the remaining two subjects. Muscle oxidative capacity (19.5 +/- 5.1 microL O2/min) for patients with end-stage renal failure was not different from values for those who had undergone renal transplantation, but was lower than values found in trained athletes.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle histology in becker muscular dystrophy

Twenty patients with Becker muscular dystrophy (BMD), confirmed by dystrophin tests, were studied histologically. There were several morphological differences between younger (less than or equal to 15-year-old) and older (greater than 15-year-old) patients. In the younger patients, active muscle fiber necrosis followed by a regenerating process was conspicuous. In the older patients, the active degenerative changes appeared less prominent and, instead, more chronic myopathic changes such as moth-eaten fibers, fiber splitting, and hypertrophic fibers were evident. These age-dependent differences in the pathology of BMD were irrespective of the duration of clinical symptoms, i.e., BMD patients of a similar age showed a similar morphological feature regardless of age at onset. Although the presence of mild fiber type grouping and some small angulated atrophic fibers suggested a certain degree of neurogenic involvement, none of biopsies showed significant grouped atrophy as seen in neuropathic disorders. There was no correlation between the histological changes and the specific dystrophin abnormality.

Fiber type composition of the human male trapezius muscle: Enzyme‐histochemical characteristics

The human trapezius muscle has an origin that is more extensive than that of any other body muscle; it has a complex macroscopic structure with fibers running in different directions. Histochemical analysis of multiple samples, obtained from different parts of the trapezius muscle from five males, showed marked differences in the distribution and the cross-sectional fiber area of the fiber types among different parts of the muscle as well as among individuals. As revealed by the mATPase activity, after different levels of alkaline and acidic preincubations, the lower third of the descending portion, the transverse, and the ascending portions of the muscle had a predominance of type I fibers (low mATPase activity at pH 9.4), whereas the most superior parts of pars descendens had a higher frequency of type II fibers (high mATPase activity at pH 9.4). The fibers of the most superior parts of the muscle were considerably smaller compared with those in all the other parts. In sections stained for NADH-TR, moth-eaten fibers were observed within parts of the descending portion. Their location and their larger fiber area, compared with that of ordinary type I fibers, may be related to frequent and/or continuous use of these fibers. In conclusion, the differences in fiber type composition between the different parts of the muscle probably reflect different functional demands on the trapezius muscle in various head, neck, and shoulder movements. We suggest that the interindividual differences in muscle fiber composition are due, at least in part, to genetic factors.

Fibre-type composition, structure and cytoskeletal protein location of fibres in anterior tibial muscle

Muscle biopsies were obtained from the anterior tibial muscle (TA) of 15 healthy, sedentary young (23-37 years) and 13 healthy and physically active elderly (66-77 years) volunteers. The mean frequency of type I fibres was lower in the young subjects compared with the elderly, but the mean type I fibre cross-sectional area was equal in the two groups. The type IIA fibres were, however, smaller in the elderly than in young subjects. Capillary density, capillary per fibre ratio, capillaries in contact with type I fibres (CC) and CC in relation to type I and type II fibre area did not differ in the two groups. The number of capillaries in contact with type IIA fibres was higher in the younger group. Only occasional and minor pathological changes were observed in the young subjects. In the elderly, such changes were much more common, including central nuclei, ring fibres, fibre splitting, scattered highly atrophic fibres, moth-eaten fibres and vacuoles. Ring fibres were most easily identified with anti-desmin labelling and highly atrophic fibres exhibited a rough network of labelling. Increased content of actin and spectrin was also observed at the periphery of ring fibres. In the elderly group, a qualitative ultrastructural analysis was also obtained and obvious changes included some myofilament loss, collections of lipofuscin which were also observed in satellite cells, proliferation of the SR-T systems and increased wrinkling of nuclear membranes and sarcolemma.

Muscle biopsy in AIDS and ARC: Analysis of 50 patients

We report a large spectrum of histological muscle abnormalities in 50 homosexual men with AIDS and ARC. We encountered moth-eaten fibers in 76%, angulated fibers in 76%, type groupings in 62%, type 2 fiber atrophy in 58%, mononuclear endomysial and/or perimysial and/or perivascular infiltrates in 36%, necrosis and phagocytosis in 30% and target fibers in 6%. Two patients showed vasculitis and two others showed perifascicular atrophy. On the whole, 96% of the biopsies showed substantial abnormalities. Muscle involvement in AIDS seems more common than previously suspected.

Reversible emetine-induced myopathy with ECG abnormalities: a toxic myopathy

A young anorexic woman is described with a history of progressive muscle weakness following chronic ingestion of syrup of ipecac that was used in an attempt at weight control. Electrocardiogram (ECG) showed T-wave inversion in all leads and prolongation of the Q-T interval. Electromyography was abnormal. Muscle biopsy revealed a randomized, generalized, predominantly type-2 fibre atrophy and structural alterations in oxidative enzyme stains, such as targetoid and moth-eaten fibres. A few necrotic cells were actively phagocytosed. Electron microscopy revealed severe sarcomeric abnormalities with Z-line streaming, myofibrillar disorganization and increased lysosomal activity. After discontinuation of ipecac syrup, the patient noted a gradual improvement in her condition. The ECG became normal. Emetine and related drug-induced myopathies are uncommon but are of experimental interest because of their effects on mitochondria and the light they shed on autophagic mechanisms in muscle.

Muscle function and morphology in myotonic dystrophy.

Patients with myotonic dystrophy classified clinically into function groups were studied. Muscle strength for knee extension and flexion was, with few exceptions, moderately or markedly reduced with successively more severe clinical disability. The reduction in maximal walking speed showed a similar tendency. There was a large percentage of both type I and in relation to normal findings of type II C fibers in biopsies from most patients. The fiber area varied greatly even in the patients in the best function groups, some of whom had large type II fibers. The most common-histopathological changes, found in all function groups, were fiber atrophy with small angular fibers, internal nuclei, splitting, fibrosis and moth-eaten fibers. A high percentage of type I fibers can already be seen in patients with practically no other morphological changes and without significant functional deterioration.

Histochemical analysis of rat masticatory muscles--effects of surgical detachment and reattachment

The effects of tenotomy and reattachment on the rat masticatory muscles, masseter and digastric muscle, were analyzed histochemically. The distribution of each muscle fiber type classified by ATPase staining and the oxidative capacity detected by NADH-TR staining were examined and were compared with those of the control group.The mosaic pattern of the type 2A and type 2B fibers was found in the external part while the type 2A fiber was mostly found in the internal part of the anterior deep masseter of the control group. On the other hand, in the digastric muscle, the mosaic pattern of the type 1, type 2A and type 2B fibers was found in the internal part and the mosaic pattern of the type 2A and type 2B fibers was observed in the external part. These histochemical characters of the rat masticatory muscles might be related to the physiological characters of the rat jaw movement.Numerous moth-eaten fibers, which shown degenerative changes in the muscle fibers, were observed histochemically immediately after tenotomy, however these changes recoverd gradually and only a few such changes were found at 20 days after tenotomy. There seemed to be no relation between the appearance of the moth-eaten fibers and the type of muscle fibers. The intensity of these degenerative changes in the muscle fibers was found to be less in the reattach-ment group of digastric muscle than in the tenotomy group.The possibility of the surgical detachment or the reattachment of the masticatory muscles during orthognatic surgery was discussed.

“Ragged-red” fibres in myotonic dystrophy

Twenty-five muscle biopsies (18 from the left biceps and 7 from the left quadriceps) of 25 patients suffering from myotonic dystrophy (MyD) were studied, 13 of which showed “ragged-red” fibres (RRFs); all the RRFs, which were type I fibres, were found in biceps muscles, while none of the quadriceps muscles showed RRFs. The incidence of RRFs varied from 0.5% to 20.0% (average 4.2%). On electron microscopy, RRFs contained enlarged mitochondria, usually in subsarcolemmal clusters, including dense granular matrix materials, concentrically whired membranous cristae, and paracrystalline inclusions, consistent with those of previously reported cases of mitochondrial myopathy, suggesting that RRFs observed in biopsies from patients with MyD are due to abnormal mitochondria. The biopsy findings indicative of MyD including pyknotic nuclear clumps, moth-eaten fibres, ring fibres, type I fibre atrophy, and type I fibre predominance, were much more common findings in biceps muscles than quadriceps muscles, and in biopsies with RRFs than those without RRFs. From our observations, it is possible that RRFs in biopsied muscles from patients with MyD are not incidental observations but are intimately associated with the pathogenesis of this disorder, and that RRFs may be a special form of pathological reaction in which accumulation of abnormal mitochondria occurs.

Response of the diaphragm muscle to electrical stimulation of the phrenic nerve

The histological, histochemical, and ultrastructural features of canine diaphragms subjected to pacing by high-frequency electrical stimulation (27 to 33 Hz) of the phrenic nerve are compared with unstimulated diaphragms and with diaphragms subjected to pacing by low-frequency stimulation (11 to 13 Hz). The high-frequency group showed a reduced tidal volume (fatigue) after long-term stimulation, and myopathic changes which included enlarged internal and sarcolemmal nuclei, ring fibers, moth-eaten fibers with irregular histochemical staining, core/targetoid fibers, and smearing and aggregation of Z-band material with electron microscopy. The low-frequency group did not develop a significant degree of fatigue or pathological changes, and showed histochemical evidence of transformation to fast-twitch (type II) fibers. Possible pathogenic mechanisms and their similarity to those in certain human neuromuscular diseases are discussed. The application of the findings resulting from high- and low-frequency stimulation to long-term diaphragm pacing in humans with chronic ventilatory insufficiency is also discussed.

A histological and histochemical study of changes of fiber types in experimental myotonia.

In both fast and slow muscles of rats treated with 20--25 diazacholesterol there were qualitative alterations, such as changes of fiber outlines, numerous moth-eaten fibers and rare ring fibers. In addition there were generally larger groups of Type I and intermediate fibers than in normal controls ("type-grouping" tendency) in the preparations for oxidative enzymes in the extensor digitorum longus (EDL) of myotonic animals. Quantitative evaluations of EDL and soleus of myotonic rats revealed moderate hypothrophy of Type I and Type II fibers with an increase in the numbers of Type I and of Type III fibers in the EDL and a significant decrease of the nondominant fibers in the soleus muscle. The data are discussed in the light of a neurally mediated and/or direct action of the drug on the muscle fiber.

The early effects of ischemia upon skeletal muscle mitochondria

The effects of early ischemia were studied in the anterior tibial muscle of Sprague-Dawley rats after 2–24 hr of tourniquet compression at the thigh. Ragged-red fibers, moth-eaten fibers, cores and targets were seen in tissue examined by enzyme histochemistry and electron microscopy. Giant mitochondria, abnormalities of cristal arrangement, crystalloids, osmiophilic inclusion bodies and myeloid figures were dominant features of the mitochondrial reaction. The results of this experiment indicate that early ischemia induces a variety of changes described in other neuromuscular conditions such as dystrophy and the “mitochondrial myopathies.” The pathogenesis of these changes and their relationship to human disease of muscle is discussed.